DESCRIPTION: (Applicant's Abstract) This grant application describes a research program, which demonstrates a novel strategy for the efficient chemical synthesis of oligosaccharide structures bearing anticancer, cardiotonic, and antimicrobial activity. The research described effectively couples stereoselective methods for glycoside formation from glycals with a novel method for the synthesis of carbohydrate glycals via a novel alkynol cycloisomerization transformation discovered in the Principal Investigator's laboratories. This unique approach has many advantages over classical synthetic methods when applied to the construction of oligosaccharides bearing unusual or unnatural stereochemical and substitution patterns, as well as the highly deoxygenated carbohydrate oligosaccharides present in many compounds exhibiting anticancer and other therapeutic properties. Specific aims of this research plan include: (1) development of new reagents and catalysts for endo -selective cycloisomerization of alkynyl alcohols; (2) synthesis of the trisaccharide moiety of cardiotonic steroids; (3) parallel synthesis methodology for preparing libraries of glycoconjugate analogs of compounds exhibiting anticancer and other biological activities; and (4) synthesis of glycoside linkages exhibited in the antimicrobial saccharomicin heptadecasaccharides, leading to a total synthesis of saccharomicin A.